1HH6

ANTI-P24 (HIV-1) FAB FRAGMENT CB41 COMPLEXED WITH A PEPTIDE

Summary for 1HH6

• Entry DOI: 10.2210/pdb1hh6/pdb
• Related: 1BOG 1CFN 1CFS 1CFT 1HH9 1HI6
• Descriptor: IGG2A KAPPA ANTIBODY CB41 (LIGHT CHAIN), IGG2A KAPPA ANTIBODY CB41 (HEAVY CHAIN), PEP-4, ... (4 entities in total)
• Functional Keywords: antibody/peptide, polyspecificity, crossreactivity, fab-fragment, hiv-1, immune system
• Biological source: MUS MUSCULUS (HOUSE MOUSE); More
• Total number of polymer chains: 3
• Total formula weight: 47756.47

Authors

Hahn, M.,Wessner, H.,Schneider-Mergener, J.,Hohne, W. (deposition date: 2000-12-21, release date: 2001-01-26, Last modification date: 2024-11-06)

Primary citation

Hoffmuller, U.,Knaute, T.,Hahn, M.,Hohne, W.,Schneider-Mergener, J.,Kramer, A.
Evolutionary Transition Pathways for Changing Peptide Ligand Specificity and Structure
Embo J., 19:4866-, 2000

PubMed Abstract: We identified evolutionary pathways for the inter- conversion of three sequentially and structurally unrelated peptides, GATPEDLNQKL, GLYEWGGARI and FDKEWNLIEQN, binding to the same site of the hypervariable region of the anti-p24 (HIV-1) monoclonal antibody CB4-1. Conversion of these peptides into each other could be achieved in nine or 10 single amino acid substitution steps without loss of antibody binding. Such pathways were identified by analyzing all 7 620 480 pathways connecting 2560 different peptides, and testing them for CB4-1 binding. The binding modes of intermediate peptides of selected optimal pathways were characterized using complete sets of substitution analogs, revealing that a number of sequential substitutions accumulated without changing the pattern of key interacting residues. At a distinct step, however, one single amino acid exchange induces a sudden change in the binding mode, indicating a flip in specificity and conformation. Our data represent a model of how different specificities, structures and functions might evolve in protein-protein recognition.

PubMed: 10990450
DOI: 10.1093/EMBOJ/19.18.4866

Experimental method

X-RAY DIFFRACTION (2.6 Å)